Amadeus reinvests heavily in R&D, with a spend equivalent to its #3 competitor's total revenue. This creates a widening technology and product gap that smaller players cannot bridge, fortifying its market leadership and making it increasingly difficult for others to keep up.

Causeway Therapeutics strategically targets a market with no existing FDA-approved drugs. By focusing on conditions like tennis elbow, where the standard of care is limited, they are creating a new therapeutic category rather than competing in a crowded space, giving them a unique market position.

Many medtech companies design large trials where a tiny, clinically meaningless response can be statistically significant. Dr. Holman advises entrepreneurs to instead run rigorous trials that prove genuine clinical value, arguing that credible data is the ultimate moat, even if it carries a higher risk of failure.

Unlike cryopreserved cell therapies, Orca Bio's fresh-cell treatment operates on a strict 72-hour timeline from donor to patient. This complex logistical requirement, demanding tight coordination with donor centers and hospitals, serves as a significant operational barrier to entry for potential competitors, creating a durable advantage.

Instead of competing directly with an established drug, companies can target a non-overlapping, genetically defined patient population. Idea Biosciences' drug for uveal melanoma is for HLA A2-negative patients, while the approved drug KimTrac is for HLA A2-positive patients. This strategy allows for market entry without a head-to-head battle.

While patents are important, a pharmaceutical giant's most durable competitive advantage is its ability to navigate complex global regulatory systems. This 'regulatory know-how' is a massive barrier to entry that startups cannot easily replicate, forcing them into acquisition by incumbents.

A competitive moat can be built by moving beyond simple service delivery (e.g., shipping medicine) to a closed-loop system. This involves diagnostics to establish a baseline, personalized treatment plans based on results, and ongoing re-testing to demonstrate improvement, creating a sticky user journey.

Investing in clinical studies is not just for product validation; it's a powerful marketing strategy. It allows you to make scientifically-backed claims in ads that competitors cannot legally replicate, creating a significant and sustainable competitive advantage.

Ocular Therapeutix's trial prioritized a primary endpoint designed to satisfy FDA requirements for a superiority label—a key regulatory win. However, the CEO stresses that clinicians use different metrics like OCT fluid, where their drug "easily beat Eylea." This highlights a crucial strategy: separate the endpoint needed for approval from the data that drives physician adoption.